Reduced IGF-1 Levels Following Clomiphene Treatment for Male Hypogonadism

madman

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* IGF-1 measured by LC-MS before and after clomiphene therapy.




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Abstract

Context


The selective estrogen receptor modulator clomiphene stimulates pituitary-derived gonadotropins to generate sex steroids including estrogen. Estrogen activates SOCS-3 which can inhibit growth hormone-directed JAK/STAT signaling to reduce serum IGF-1 levels.


Objective

We sought to examine the effects of clomiphene therapy on IGF-1 levels in non-acromegalic male patients treated with clomiphene for underlying hypogonadism.


Design

We identified 20 male hypogonadal subjects treated with clomiphene citrate for at least three months.


Setting

These patients were treated in an ambulatory, academic, tertiary medical center.


Patients

The 20 male patients ranged from 27-76 years of age and hypogonadism was due to several etiologies, including prolactinomas, clinically non-functioning pituitary tumors, rathke’s cleft cysts, colloid cysts or idiopathic causes.


Intervention

Clomiphene citrate 50 mg three days per week was administered for a minimum of three months.


Main Outcome measure(s)

IGF-1 measured by LC-MS before and after clomiphene therapy.


Results

15 of 20 (75%) of hypogonadal men treated with clomiphene exhibited a decrease in median (IQR) serum IGF-1 levels of -0.60 (-1.2 - 0.0) (p<0.01). Two of the 20 patients (10%) exhibited a decrease in IGF-1 > 2 standard deviations below their age- and sex-matched mean value.


Conclusions

Clomiphene therapy can result in a significant reduction in serum IGF-1 levels in some treated hypogonadal men. Given that the decrease in IGF-1 can be >2 SD in some patients and potentially clinically significant, we recommend interval monitoring of serum IGF-1 levels and symptoms of growth hormone deficiency in hypogonadal patients treated with clomiphene citrate.
 

Attachments

Figure 2. a. Box plot depiction of trend in IGF-1-SD after clomiphene citrate initiation. ** p<0.01. b. Estimation plot depiction of trend in IGF-1-SD before and after clomiphene citrate initiation.

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Figure 3. a. Box plot depiction of trend in total testosterone (TT) after initiation of clomiphene citrate. Pre-TT: Total testosterone before clomiphene initiation; Post-TT: total testosterone after clomiphene initiation. b. Estimation plot depiction of trend in total testosterone (TT) after initiation of clomiphene citrate. Pre-TT: Total testosterone before clomiphene initiation; Post TT: total testosterone after clomiphene initiation. **** p<0.001.

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Figure 4. a. Box plot depiction of trend in free testosterone (FT) after initiation of clomiphene citrate. Pre-FT: Free testosterone before clomiphene initiation; Post-FT: free testosterone after clomiphene initiation. b. Estimation plot depiction of trend in free testosterone (FT) after initiation of clomiphene citrate. Pre-FT: free testosterone before clomiphene initiation; Post-FT: free testosterone after clomiphene initiation. *p<0.05.

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Scientific Reference

Lakshman KM, Kaplan B, Travison TG, Basaria S, Knapp PE, Singh AB, LaValley MP, Mazer NA, Bhasin S. The effects of injected testosterone dose and age on the conversion of testosterone to estradiol and dihydrotestosterone in young and older men. J Clin Endocrinol Metab. 2010 Aug;95(8):3955-64.

DOI: 10.1210/jc.2010-0102 | PMID: 20534765 | PMCID: PMC2913038

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